At age 15, as a student reporter, Van Ark met and interviewed actress Julie Harris, who later recommended Van Ark apply to the Yale School of Drama. Harris had been the youngest student to attend the school on scholarship. Van Ark was one of the few students to attend the graduate program without first having earned an undergraduate degree. She attended for only one year. Years later, Harris appeared on Knots Landing as Lilimae Clements, the mother of Valene Ewing, Van Ark's character.[7][8]

After receiving a contract with Universal Studios, Van Ark co-starred with Bette Davis in The Judge and Jake Wyler, a 1972 television pilot that failed to be picked up by NBC. Van Ark was also a regular castmember of the short-lived television sitcoms Temperatures Rising (1972–73) and We've Got Each Other (1977–78). After working for several years in a variety of guest roles on television, she gained her best-known role as Valene Ewing (originally as a one-time guest appearance on Dallas) in 1978. However, writers later worked the character into a couple of additional episodes; she then carried the character over into the long-running spin-off Knots Landing in 1979. She remained with Knots Landing for thirteen of the show's fourteen seasons, leaving in 1992 (although she did return for the series' final episode in May 1993). In the storyline, Valene was married three times to husband Gary Ewing (played in the series by Ted Shackelford), and had two other marriages during the show's run.

During her thirteen seasons on Knots Landing, Van Ark earned two Soap Opera Digest Awards for Best Actress and was nominated a further six times. She also directed two episodes of the series. Van Ark and co-star Michele Lee became good friends while working on the series, mirroring their characters' onscreen friendship. In May 1997, she reprised her role of Valene Ewing in the CBS mini-series, Knots Landing: Back to the Cul-de-Sac, while in December 2005, she appeared in the non-fiction reunion Knots Landing Reunion: Together Again in which she reminisced with the other cast members of the long running CBS television show.

After leaving Knots Landing, she starred in an ill-fated pilot called Spin Doctors, a sitcom for NBC that was not picked up. In addition, she originated the role of Gloria Fisher Abbott on CBS television's The Young and the Restless from 2004–2005, then decided to leave the role and was replaced by Judith Chapman.

In April 2001, Van Ark was featured in an episode of the Howard Stern-produced show Son of the Beach as Ima Cummings, the mother of show regular BJ Cummings (played by Jaime Bergman). In 2008, she was reunited with her Knots Landing co-star Donna Mills in an episode of the FX drama series Nip/Tuck. The same year, she also played a network executive in the film Channels.

In 2011, she performed voice work in an episode of the animated comedy series Archer. In 2013, she reprised her role as Valene Ewing, guest-starring in an episode of the new Dallas series. The same year she also appeared as a guest judge on the Logo series RuPaul's Drag Race.

^Garfield, David (1980). "Appendix: Life Members of The Actors Studio as of January 1980". A Player's Place: The Story of The Actors Studio. New York: MacMillan Publishing Co., Inc. p. 280. ISBN0-02-542650-8.